1. Introduction to General Pathology and Pathophysiology. Role in the biomedical disciplines - Health and disease status - Homeostasis as a balance between opposite actions - Health status as a balance point - The method: way to go - General etiology: genetic, epigenetic and environmental causes of disease - Terminological issues in medicine and dentistry - The global burden of disease - Main causes of death and disease in developed countries towards developing countries - Concept of pathogenesis - Competition between diseases and life expectancy at birth.
2. Cellular pathology. Cell damage and death. Causes of cell damage. Morphological alterations in cell damage: reversible damage, necrosis. Mechanisms of cell damage: ATP depletion, mitochondrial damage, intracellular entry of calcium and loss of calcium homeostasis, accumulation of reactive species and oxygen free radicals, membrane permeability defects, DNA and protein damage. Ischemic and hypoxic damage. Chemical damage. Apoptosis: causes of apoptosis, morphological and biochemical changes in apoptosis, apoptosis mechanisms, apoptosis in physiological and pathological conditions. Autophagy. Intracellular accumulations. Pathological calcification. Cellular aging.
3. Genetic diseases. Architecture and functions of the human genome. Mutations. Epigenetic alterations. Mendelian diseases. Complex multigenic diseases. Chromosomal alterations and chromosomal diseases. Diseases with atypical monogenic inheritance. Molecular diagnosis of genetic and epigenetic diseases.
4. Acute and chronic inflammation. NFkB, self and non-self recognition. Background. Acute inflammation: stimuli of acute inflammation, reaction of blood vessels in acute inflammation, reaction of leukocytes in inflammation, extinction of the acute inflammatory response. Inflammatory mediators: cell-derived mediators, mediators derived from plasma proteins. Outcomes of acute inflammation. Morphological aspects. Chronic inflammation: causes, morphological characteristics and cellular responses. Granulomatous inflammation. Systemic effects and consequences. Temperature.
5. Renovation, regeneration and tissue repair. Control of tissue proliferation and homeostasis: proliferative activity of tissues, stem cells and their role in tissue homeostasis. Growth factors and proliferative and anti-proliferative signals. The "checkpoints" of the cell cycle. Mechanisms of tissue and organ regeneration. Extracellular matrix and cell-matrix interactions. Repair healing, healing and fibrosis: angiogenesis, healing of skin wounds, local and systemic factors affecting wound healing, pathological aspects of wound healing, fibrosis.
6. Tissue adaptations to damage. Physiological and pathological hyperplasia and hypertrophy. Atrophy, aplasia and hypoplasia. Metaplasia. Dysplasia.
7. Neoplastic diseases. Molecular basis of cell transformation. Oncogenes, antioncogenes: their role in the mechanisms that control neoplastic transformation. Viral and cellular oncogenes: homologies and differences. MicroRNA and tumors. Metabolic factors and Warburg effect in cell transformation. Sporadic and hereditary tumors. Examples of autosomal dominant syndromes. Benign and malignant tumors. General histogenetic classification. Oral and nasopharynx tumors: characteristics and risk factors. Molecular mechanisms involved in invasion and metastasization: general concepts. Primitive and metastatic tumors. Pathways of metastasization. Staging concepts. Elements of tumor epidemiology. Immunity and tumors. Antigens and tumor markers. Elements of tumor therapy. Environmental and chemical carcinogenesis. Cancer initiation and promotion concepts. Main direct and indirect chemical carcinogens. Carcinogenesis from ultraviolet and ionizing radiation. Tobacco and cancer. Viral carcinogenesis. Oncogenic virus-induced transformation to DNA and RNA. Acute and chronic transforming retroviruses. Oncogenic viruses in human tumors: papilloma virus, herpesvirus, hepatitic viruses, HTLV1 and HIV.
8. Infectious diseases. Parasitism, infection, infestation, intoxication. Evolutionary adaptations in pathogenic host-micro-organism relationships. Socio-cultural and environmental factors implicated in the origin and spread of infectious diseases. Routes of transmission of infectious agents. Arthropod vectors. Mechanisms and barriers of natural defense and cellular and tissue response to pathogens in different external and internal surfaces. Immunization. Virulence factors. Eso and endotoxins. Endotoxic shock: definition, risk factors and pathogenetic mechanisms. Bacterial infectious diseases. Chronic granulomatous infections. Syphilis, tuberculosis, leprosy. Rickettsial and chlamydial infections. Viruses as a cause of disease. Damage mechanisms. Main viral infections. Critical periods for embryo-fetal infectious damage. Herpesvirus infections. Main fungal infections. Main protozoan diseases. Notes on helminth pathologies (main infestations with nematodes, trematodes, cestodes) Notes on ectoparasitic arthropods. So-called prion diseases. Molecular pathophysiology of prion infections. Concept of prion and history of discovery. Exogenous, endogenous and hereditary prion diseases.
9. Hemodynamic diseases, atherosclerosis, thromboembolic disease and shock. Edema, hemorrhage, hemostasis and thrombosis. Coagulation mechanisms and their alterations. Atherosclerosis: pathogenic characteristics and mechanisms. Thrombosis. Embolism. Heart attack. Shock.
10. Environmental and nutritional pathologies. Diabetes. Obesity. Metabolic syndrome. Damage from physical and mechanical causes. Radiation. Acute and chronic damage from exciting radiation. Acute and chronic damage from ionizing radiation. Other radiation from the electromagnetic spectrum. Freezing. Burns. Trauma.
11. Introduction to the immune system. General properties and components of the immune system
12. Innate immunity. Recognition of microorganisms by innate immunity. Components of innate immunity. Evasion of innate immunity by microorganisms. Role of innate immunity in the activation of adaptive immunity.
13. Capture and presentation of antigen to lymphocytes. Characteristics of antigens recognized by T lymphocytes. Capture of protein antigens by cells presenting the antigen. Major histocompatibility complex. Protein antigen processing. Characteristics of antigens recognized by B lymphocytes
14. Recognition of antigen by adaptive immunity. Lymphocyte antigen receptors. Development of immunological specificities.
15. Cell-mediated immune response. Antigen recognition and costimulation. Biochemical pathways of transduction in the activation of T lymphocytes. Functional responses of T lymphocytes to antigens and costimulatory molecules.
16. Effector mechanisms of cell-mediated immunity. Cell-mediated responses. Migration of effector T lymphocytes to the infection site. Effector functions of T helper CD4 + lymphocytes. Effector functions of CD8 + cytotoxic T lymphocytes. Resistance of pathogenic mechanisms to cell-mediated immunity.
17. Humoral immune response. Activation of B lymphocytes by the antigen. Role of CD4 + T helper lymphocytes in the humoral response. Antibody response to T-independent antigens. Regulation of the humoral immune response: antibody feedback.
18. Effective mechanisms of humoral immunity. Properties and effector functions of antibodies. Neutralization of microorganisms and microbial toxins. Reactions mediated by eosinophils and mast cells. Opsonization and antibody-mediated phagocytosis. Antibody-dependent cellular cytotoxicity. Activation of the complement system. Antibody functions in particular anatomical sites. Evasion of humoral immunity by microbes.
19. Tolerance and autoimmunity. Lymphocyte tolerance T. Lymphocyte tolerance B. Principle autoimmunity and pathogenesis. genetic factors of autoimmunity. Role of infections in autoimmunity.
20. Immunity against transplants. Immune responses against transplants.
21. Hypersensitivity. Hypersensitivity reactions. Diseases caused by antibodies and immune complexes. Diseases caused by T lymphocytes
22. Congenital and acquired immunodeficiencies. Primary congenital immunodeficiencies. Secondary congenital immunodeficiencies. Acquired immunodeficiency syndrome.
